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J Leighton

Publications and source records attributed to J Leighton.

At least 73 records · Page 4Linked to original sources
PubMed1977

Development of tissue culture procedures for predicting the individual risk of recurrence in bladder cancer.

We are using three correlated approaches in tissue culture to develop procedures for distinguishing between histologically similar tumors and to develop distinctions that we hope can be correlated with a favorable outcome or with recurrence of more serious disease. Our procedures involve study of the growth of resected tumor tissue in a three-dimensional matrix of collagen-coated cellulose sponge. Using bladder cancer cell lines we are also studying the patterns of cytotypic zonation that appear in response to prolonged exposure to continuous gradients of oxygen tension and of temperature. Finally, we are using vitamin A and modifiers of cyclic adenosine 3':5'-monophosphate as molecular probes to alter the morphological expression of tumors in matrix and in gradient cultures. We have studied over 80 specimens of clinical cancer in matrix culture. Tumors of similar histopathology grow with distinctly different architecture in the matrix of collagen-coated sponge. We must now determine whether these patterns in vitro can be correlated with the course of individual patients.

Carcinoma, Transitional Cell↗
PubMed1976

Histological comparison of the growth of rat bladder carcinoma R-4909 observed for two years in vitro and in vivo.

A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We report here observations made during the first 2 years of an ongoing study on the divergent histopathology of R-4909 under several conditions of propagation. During the entire period, the tumor has been maintained by serial passage in rats (Fischer 344) and by serial passage in vitro. At intervals, cells of the tissue culture series were inoculated into rats to compare the histopathology of animal- and culture-passed strains. We obtained several clones from the stock cultures and these also were maintained continuously in vitro. At intervals, cells from two of these lineages, clone A and clone B, were inoculated into rats. After 2 years, cells maintained in stock culture, on injection into new rats, produced growths similar to the original in that all three epithelial patterns, transitional, squamous, and adenomatous, were perpetuated. In contrast, the tumor passed exclusively in vivo lost its squamous component completely. It became anaplastic, with tissue architecture almost entirely adenomatous and cystic. Unlike the stock tissue culture line, the clonal isolates following prolonged culture produced adenomatous tumors only. In a related preliminary study, we inoculated into rats R-4909 cells that had been cultivated for up to 2 months under aerobic and anaerobic conditions. Tumors grew in most of the animals, and those of the aerobic group were more cystic than the others.

Animals↗
PubMed1976

Conditions of cultivation required for the formation of hemicysts in vitro by rat bladder carcinoma R-4909.

Rat urinary bladder carcinoma R-4909 grew readily in vitro. In areas where saturation density occurred in the cultures, occasional hemicysts were observed. A modification of technique producing "packed cultures" resulted in the appearance of greater numbers of hemicysts. Four clonal isolates of R-4909 were also studied in packed culture. Clone B formed hemicysts in abundance. Clone D produced occasional hemicysts similar to the parent stock line. No hemicysts were seen in cultures of clone A or clone C. The number of hemicysts formed by clone B in packed culture was responsive to the ratio between cell number and volume of medium, to serum concentration in the medium, and to pH of the medium. The last was of particular interest since a pH of 7.8 enhanced and a pH of 6.6 inhibited hemicyst formation. The effects were all reversible. On scanning electron microscopy, we found well-developed cell membrane structures between contiguous cells. In media with sufficient serum for hemicyst formation, the articulations between cells were prominent. With low serum concentrations, hemicysts did not form and the intercellular articulations were less distinct. We interpret the formation of hemicysts as an expression of fluid transport by epithelia, a function that requires a constellation of differentiated characteristics within cells and in their level of integrated association.

Animals↗
PubMed1975

Vitamin A inhibition of keratinization in rat urinary bladder cancer cell line Nara Bladder Tumor No. 2 in meniscus gradient culture.

The Nara Bladder Tumor No. 2 cell line, established from a urinary bladder carcinoma in the Wistar rat, formed keratinizing cells and multicellular pearls in meniscus gradient culture when fed with a medium of 15 or 30% fetal calf serum in Eagle's minimal essential medium. Confluent monolayer cultures were first prepared with the tubes in conventional horizontal position. When cultures were then changed to a vertical position, stratification, piling up, and aggregation of cells were observed in a few days at the aerobic end of the gradient. Keratinization appeared 1 week after the tubes were placed in vertical position. Squamous differentiation proceeded to the formation of keratin pearls, a phenomenon never observed so distinctly and in such abundance in horizontal culture. Supplements of vitamin A, as low as 1 IU/ml, added to the medium did not inhibit piling up or aggregation but did prevent keratinization. Inhibition of keratinization by vitamin A was reversible. After vitamin A was removed from the medium, the cells in the aggregates progressed to keratinization.

Animals↗
PubMed1975

Bladder calculi and urothelial hyperplasia with papillomatosis in the rat following insertion of chalk powder in the bladder cavity with subsequent trauma of the bladder wall.

A suspension of chalk powder was injected into the cavity of the urinary bladder of Fischer 344 rats. Three weeks later rats were divided into 4 major groups and were given a submucosal injection. One group received a suspension of viable Chapman 4909 tumor cells, the 2nd group received a suspension of frozen-killed 4909 tumor cells, the 3rd group received a suspension of normal rat spleen cells, and the 4th group received cell-free fresh tissue culture medium. After 3 additional weeks urolithiasis was recognized in each experimental group. The incidence of calculi in the groups as listed above was 14 of 17, 6 of 11, 6 of 11, and 2 of 15, respectively. In control studies inocula consisted of tumor alone, i.e., without chalk powder. Inoculation of the 4909 rat bladder cancer cell line into the lumen of urinary bladders of rats did not result in any calculi after 3 weeks but did produce intramural tumor nodules and hyperplastic changes in adjacent host urothelium in 2 of 10 rats. The tumor inoculated in the submucosa of the bladder produced calculi and papillomas in 2 of 7 rats, and it produced intramural tumor nodules with adjacent hyperplasia of urothelium in all 7 rats.

Calcium Carbonate↗
PubMed1970

Growth in vitro of cells from hyperplastic nodules of liver induced by 2-fluorenylacetamide or aflatoxin B1.

Cell suspensions obtained from hyperplastic nodules induced in rat liver by either of the two hepatic carcinogens, 2-fluorenylacetamide or aflatoxin B(1), show growth when cultured in vitro. No growth of cells from liver adjacent to the hyperplastic nodules or from liver of control rats has been obtained so far under comparable conditions. Hepatocarcinoma cells induced by 2-fluorenylacetamide grow readily in vitro but behave differently. These findings suggest that some nonmalignant cells capable of growth in vitro arise during liver carcinogenesis prior to the appearance of unequivocal cancer. Cultures of such cells may offer new avenues for the study of liver carcinogenesis.

Aflatoxins↗
PubMed1969

Secretory activity and oncogenicity of a cell line (MDCK) derived from canine kidney.

A cell line (MDCK) of dog kidney origin grows on a glass surface as a mosaic of epithelium with many multicellular hemispherical vesicles. The cells lining the blisters actively secrete into the cyst cavities. Suspensions of these cells injected intravenously in the chick embryo produce brain metastases resembling adenocarcinoma.

Adenocarcinoma↗